{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:21:04Z","timestamp":1793121664950,"version":"4.5.0"},"reference-count":20,"publisher":"Wiley","issue":"2-3","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Diverse extracellular vesicles (EVs) are present in all body fluids; however, knowledge of large EVs (lEVs) remains limited. Molecular EV profiles vary depending on EV size and the physiological circulatory system, even within the same patient. In this study, we aimed to characterize the proteomic profile of IEVs in ovarian cancer patients and identify lEV\u2010protein biomarkers. We collected tissue, serum, and ascites from patients with high\u2010grade serous ovarian cancer and concurrently separated small EVs (sEVs) and lEVs through sequential multistep centrifugation. Proteomic analysis of tissues and EVs revealed distinct EV profiles in serum and ascites, identifying 11 lEV\u2010specific proteins in serum and 14 in ascites that were absent in sEV. Of these, seven serum\u2010specific and 10 ascites\u2010specific proteins were further analyzed using transcriptomic databases, revealing candidate diagnostic and prognostic lEV\u2010protein biomarkers. Our findings underscore the importance of size\u2010based EV separation, as particle size influences biosynthetic mechanisms, in identifying lEV\u2010specific proteins with potential diagnostic and prognostic values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This study underscores the importance of distinguishing extracellular vesicle (EV) subtypes and considering body fluid specificity in biomarker discovery.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>By isolating EVs based on size and stepwise separation and analyzing their proteomic profiles in ovarian cancer, we identified potential large EV (lEV)\u2010specific biomarkers that reflect disease pathology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings provide a foundation for lEV\u2010protein\u2013based liquid biopsy approaches that could enhance the accuracy of early detection and patient stratification. Further validation in clinical settings may pave the way for more precise and personalized ovarian cancer diagnostics.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pmic.70054","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T05:37:48Z","timestamp":1759469868000},"page":"95-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential Proteomics of Large Extracellular Vesicles in Ovarian Cancer"],"prefix":"10.1002","volume":"26","author":[{"given":"Kazuhiro","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Oncology National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Asano\u2010Inami","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"},{"name":"Institute for Advanced Research Nagoya University  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kajiyama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0789-5102","authenticated-orcid":false,"given":"Akira","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"},{"name":"Institute for Advanced Research Nagoya University  Nagoya Aichi Japan"},{"name":"Fusion Oriented Research for disruptive Science and Technology Japan Science and Technology Agency  Kawaguchi Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108352"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13918"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.638357"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.74305"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44276-024-00096-0"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12418"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12128"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","unstructured":"R. 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Clinical Oncology10(2013):211\u2013224.","DOI":"10.1038\/nrclinonc.2013.5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21590"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade6958"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06434-4"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2022.08.005"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301930"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521230113"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/21541248.2016.1215283"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0759-6_10"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13051056"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","unstructured":"G.Van Niel G.D'angelo andG.Raposo \u201cShedding Light on the Cell Biology of Extracellular Vesicles \u201dNature Reviews. Molecular Cell Biology19(2018):213\u2013228.","DOI":"10.1038\/nrm.2017.125"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djy071"}],"container-title":["PROTEOMICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.70054","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pmic.70054","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.70054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:44:00Z","timestamp":1783014240000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/pmic.70054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":20,"journal-issue":{"issue":"2-3","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/pmic.70054"],"URL":"https:\/\/doi.org\/10.1002\/pmic.70054","archive":["Portico"],"relation":{},"ISSN":["1615-9853","1615-9861"],"issn-type":[{"value":"1615-9853","type":"print"},{"value":"1615-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]},"assertion":[{"value":"2025-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}